Long noncoding RNA AFAP1­AS1 enhances cell proliferation and invasion in osteosarcoma through regulating miR­4695­5p/TCF4­ß­catenin signaling.

ABSTRACT

Long noncoding RNA AFAP1­AS1 has been shown to promote tumor progression in several human cancer types, such as thyroid cancer, tongue squamous cell carcinoma and lung cancer. However, the role of AFAP1­AS1 in osteosarcoma (OS) has not been investigated. In the present study, the expression of AFAP1­AS1 was significantly upregulated in OS tissues and cell lines. Moreover, AFAP1­AS1 expression was negatively correlated with OS patient prognosis. Besides, AFAP1­AS1 knockdown significantly inhibited the proliferation and invasion of OS cells in vitro. Furthermore, in vivo xenograft experiments indicated that AFAP1­AS1 depletion delayed tumor growth. Regarding the underlying mechanism, AFAP1­AS1 served as a sponge to repress the level of microRNA (miR)­4695­5p, which targeted transcription factor (TCF)4, a pivot effector of Wnt/ß­catenin signaling pathway. It was demonstrated that overexpression of AFAP1­AS1 inhibited the expression of miR­4695­5p, while miR­4695­5p overexpression decreased TCF4 expression and reduced activation of Wnt/ß­catenin pathway. Through rescue assays, it was demonstrated that restoration of TCF4 expression reversed the effects of AFAP1­AS1 knockdown or miR­4695­5p overexpression on OS cells. Taken together, these findings demonstrated that the AFAP1­AS1/miR­4695­5p/TCF4­ß­catenin axis played an important role in OS progression.